Homology Medicines Announces World’s First Gene Editing Clinical Trial for PKU

- IND Clearance of pheEDIT Study to Evaluate a One-Time Dose of Investigational HMI-103 Incorporating a Novel Nuclease-Free Gene Editing Approach - <

- Company Provides Update on Enrollment in Ongoing pheNIX Trial of HMI-102 Gene Therapy for Adults with PKU -

BEDFORD, MA, USA I October 12, 2021 I Homology Medicines, Inc. (Nasdaq: FIXX), a genetic medicines company, announced today the pheEDIT Phase 1 clinical trial for HMI-103, a one-time, in vivo product candidate that utilizes a gene editing approach for phenylketonuria (PKU), based on the Investigational New Drug Application (IND) clearance from the U.S. Food and Drug Administration (FDA). HMI-103 will be the world’s first gene editing candidate for PKU to enter clinical trials from Homology’s dual gene therapy and gene editing technology platform, and with the launch of pheEDIT Homology moves closer to its goal of offering solutions for both adults and pediatric patients with PKU.

“Today’s milestone is the culmination of our team’s tireless work to translate our gene editing technology from an academic discovery into a clinical program for people with PKU,” said Albert Seymour, Ph.D., Chief Scientific Officer of Homology Medicines. “Our positive preclinical data in the PKU model demonstrated phenotypic correction, and the precision of HMI-103 genome integration was confirmed in a humanized liver model, which showed no evidence of off-target mutations or unwanted on-target changes to the genome. These nonclinical data give us great confidence in initiating our Phase 1 pheEDIT trial, and we look forward to continuing to work with the PKU community on our clinical programs.”

The HMI-103 pheEDIT trial is expected to enroll up to nine patients ages 18-55 years old who have been diagnosed with PKU due to PAH deficiency. Once positive safety and efficacy results are established in the adult population, Homology plans to enroll younger patients in clinical trials. The Phase 1 dose-escalation trial is designed to evaluate three doses of HMI-103 to determine the recommended dose(s) for a future trial. In addition to safety endpoints, the trial will measure serum phenylalanine (Phe) changes.

HMI-103 is designed as a one-time administration to maximize the expression of functional phenylalanine hydroxylase (PAH) in liver cells and thus restore the natural biochemical pathway that metabolizes Phe. The product candidate was developed to specifically integrate a functional PAH gene into the genome using the natural DNA repair process of homologous recombination. In addition to expression, the integration is designed to correct the cell by inactivating at least one of the mutated genes and enable that correction to persist through cell division.

Homology expects that the first patient in the pheEDIT clinical trial will be dosed following requisite Institutional Biosafety Committee and Institutional Review Board approvals at the clinical sites. The trial will include an 82-day screening/run-in period prior to HMI-103 administration.

Homology also announced today an update from its ongoing Phase 2 pheNIX clinical trial evaluating HMI-102 gene therapy in adults with PKU. As of September 30, 2021, both doses in the trial have been generally well-tolerated and have shown evidence of biological activity, including clinically meaningful reductions in Phe levels, increases in Tyr and reductions in the Phe-to-Tyr ratio. Several new clinical trials sites have also recently been added to pheNIX for a total of 13 with more sites expected shortly. Despite increased interest, enrollment is slower than anticipated due in part to COVID-19 resurgence, and the Company anticipates providing a more detailed pheNIX update in mid-2022 when it expects to have a larger dataset.

“We continue to be encouraged by the data from our pheNIX trial and to hasten enrollment, we have expanded our Medical Affairs, Clinical Development and Operations teams to support not only pheNIX, but now pheEDIT and our Hunter syndrome gene therapy trial expected this year,” said Arthur Tzianabos, Ph.D., President and Chief Executive Officer of Homology Medicines. “The flexibility of our technology platform enables us to develop gene therapy and gene editing product candidates as potential one-time treatments, and news today of our first trial that incorporates gene editing for PKU demonstrates our ability to employ both approaches in an effort to support the PKU community.”

PKU is caused by mutations in the PAH gene, which is responsible for producing the enzyme that metabolizes Phe from dietary protein. As a result, Phe accumulates to toxic levels in the blood and brain and does not convert to melanin or the amino acid tyrosine (Tyr), a precursor to neurotransmitters. Homology’s approach to PKU with gene therapy and gene editing candidates is designed to treat both the adult and pediatric communities with one-time treatments that address the genetic cause of PKU. Since gene therapy does not integrate into the genome, it can be used in cells that are not rapidly dividing, such as an adult liver. Gene editing is designed to make a permanent correction in cells, including those that are rapidly dividing, such as a child’s liver.

About HMI-102 Gene Therapy and HMI-103 Gene Editing Product Candidates

HMI-102 is an investigational gene therapy in clinical development for the treatment of phenylketonuria (PKU) in adults. HMI-102 is designed to encode the PAH gene, which is mutated in people with PKU, and delivered via the liver-tropic AAVHSC15 vector. Homology has received Fast Track Designation and orphan drug designation for HMI-102 from the U.S. Food and Drug Administration (FDA), and orphan drug designation from the European Medicines Agency (EMA).

HMI-103 is an investigational, nuclease-free gene editing product candidate ultimately designed to treat pediatric patients with PKU, whose livers are rapidly dividing, following initial clinical trials in adults. HMI-103 also uses AAVHSC15 and is designed to encode the PAH gene flanked by homology arms, or long stretches of DNA, to target the PAH region of the genome. Using the body’s natural DNA repair process of homologous recombination, the PAH gene integrates into the genome. HMI-103 is designed to express phenylalanine hydroxylase (PAH) and integrate into the PAH gene to restore the natural biochemical pathway that metabolizes phenylalanine (Phe).

About Phenylketonuria (PKU)

PKU is a rare inborn error of metabolism caused by a mutation in the PAH gene. PKU results in a loss of function of the enzyme phenylalanine hydroxylase (PAH), which is responsible for the metabolism of phenylalanine (Phe), an amino acid obtained exclusively from the diet. If left untreated, toxic levels of Phe can accumulate in the blood and result in progressive and severe neurological impairment. Currently, there are no treatment options for PKU that target the underlying genetic cause of the disease. According to the National PKU Alliance, PKU affects nearly 16,500 people in the U.S. with approximately 350 newborns diagnosed each year. The worldwide prevalence of PKU is estimated to be 50,000 people.

About Homology Medicines, Inc.
Homology Medicines, Inc. is a clinical-stage genetic medicines company dedicated to transforming the lives of patients suffering from rare diseases by targeting the underlying cause of the disease. The Company’s lead clinical program, HMI-102, is an investigational gene therapy for adults with phenylketonuria (PKU) and additional programs focus on gene editing in PKU, lysosomal storage disorders including Hunter syndrome, paroxysmal nocturnal hemoglobinuria (PNH) and other diseases. Homology’s proprietary platform is designed to utilize its family of 15 human hematopoietic stem cell-derived adeno-associated virus vectors (AAVHSCs) to precisely and efficiently deliver genetic medicines in vivo through a gene therapy or nuclease-free gene editing modality, as well as to deliver one-time gene therapy to produce antibodies throughout the body through the GTx-mAb platform. Homology has a management team with a successful track record of discovering, developing and commercializing therapeutics with a focus on rare diseases and believes that its data, internal manufacturing capabilities and broad intellectual property position the Company as a leader in genetic medicines. For more information, visit www.homologymedicines.com.

SOURCE: Homology Medicines

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